Selective posttranslational inhibition of Ca_Vβ₁-associated voltage-dependent calcium channels with a functionalized nanobody.

ABSTRACT: Ca²⁺ influx through high-voltage-activated calcium channels (HVACCs) controls diverse cellular functions. A critical feature enabling a singular signal, Ca²⁺ influx, to mediate disparate functions is diversity of HVACC pore-forming α₁ and auxiliary Ca_Vβ₁-Ca_Vβ₄ subunits. Selective Ca_Vα₁ blockers have enabled deciphering their unique physiological roles. By contrast, the capacity to post-translationally inhibit HVACCs based on Ca_Vβ isoform is non-existent. Conventional gene knockout/shRNA approaches do not adequately address this deficit owing to subunit reshuffling and partially overlapping functions of Ca_Vβ isoforms. Here, we identify a nanobody (nb.E8) that selectively

SUBMITTER: Morgenstern TJ 

PROVIDER: S-EPMC9734117 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature